Cerebellum最新文献

Around 60% of treatment-resistant schizophrenia (TRS) patients fail conventional therapies. This study aimed to evaluate the safety and effectiveness of a combined high-definition transcranial direct current stimulation (HD-tDCS)-primed intermittent theta burst stimulation (iTBS) protocol targeting the cerebellar vermis using a randomized, sham-controlled design. Thirty-six right-handed TRS patients (aged 18-59 years) were randomized to active (n = 18) and sham (n = 18) groups. The active group received cathodal HD-tDCS (2 mA for 15 min) at the cerebellar vermis, followed by iTBS per session. Sessions were daily for 5 days/week over 2 weeks (total 10 sessions), 30 min apart. The sham group received sham HD-tDCS (0.2 mA) followed by sham iTBS. Assessments occurred at baseline, Day 14, and Day 28 using the Positive and Negative Syndrome Scale (PANSS), Schizophrenia Cognition Rating Scale (SCoRS), Modified Simpson-Angus Extrapyramidal Side Effects Scale (MSAS), CGI-S, and WHOQOL-BREF. Intention-to-treat analysis revealed significant between-group time × group interactions favored the active group for PANSS total (F = 6.196, p = 0.018, partial η²=0.170), PANSS-negative (F = 5.06, p = 0.031, partial η²=0.130), and SCoRS (F = 4.149, p = 0.049, partial η²=0.109). No significant effects for PANSS-positive (p = 0.107), PANSS-general (p = 0.175), CGI-S (p = 0.174), WHOQOL-BREF (p = 0.088), or MSAS (p = 0.935). Minor side effects reported; no dropouts from adverse events. The combined HD-tDCS-primed iTBS protocol targeting the cerebellar vermis is safe and modestly effective for overall psychopathology, negative symptoms, and cognition in treatment-resistant schizophrenia. Due to simultaneous sham control of both modalities, the specific contribution of HD-tDCS priming cannot be isolated. Future 2 × 2 factorial trials with neuronavigation are required.

Cerebellar paired associative stimulation (cPAS) is a non-invasive neuromodulation protocol that combines peripheral nerve stimulation with cerebellar transcranial magnetic stimulation to induce plasticity in the cerebellar-cortical pathway. Previous evidence suggested that cPAS delivered at a 25ms interstimulus interval (cPAS25) can modulate cerebellar-primary motor cortex connectivity, as reflected by changes in cerebellar-brain inhibition (CBI). However, its behavioural relevance remains unclear. To investigate this issue, we conducted two experiments in young healthy adults using a within-subject crossover design to compare the effects of cPAS25 and a temporally mismatched control (cPAS10). In Experiment 1, participants received cPAS followed by a visuomotor sequence learning task, with motor performance assessed via movement time, error rate, and a composite skill index. CBI and motor evoked potentials (MEPs) were recorded at baseline, post-stimulation, and after task completion. In Experiment 2, a subset of participants received cPAS without the task to isolate its neurophysiological effects. cPAS25 significantly improved motor learning compared to cPAS10, as shown by a greater increase in skill index. It also reduced CBI, but this effect was observed only when cPAS was not followed by motor practice, suggesting a task-sensitive interaction. MEP amplitudes remained unchanged, indicating selective modulation of cerebellar output. These results support a timing-dependent, context-sensitive mechanism of cerebellar plasticity. cPAS25 can enhance motor learning and modulate cerebellar-cortical connectivity, although effects may not summate when paired with motor practice. These findings highlight the translational potential of cPAS25 as a precision neuromodulatory approach to enhance motor learning and rehabilitation by targeting cerebellar circuits.

Background: Neurofibromatosis type 1 (NF1) is a genetic condition caused by pathogenic variants of the NF1 gene. While alterations in cerebral structural and microstructural differences have been reported in NF1, the cerebellum remains largely unexplored. Since individuals with NF1 are at risk for cognitive difficulties, which are in turn associated with cerebellar processes, understanding the underlying neural mechanisms is critical for intervention development.

Methods: Youth (5-16 years) with NF1 (n = 30) and unaffected youth (n = 40) participated in neuropsychological (i.e., neurocognitive, parent report of motor abilities) testing and MRI to ascertain structural cerebellar metrics, including volume and white matter mean diffusivity (MD), fractional anisotropy (FA), neurite density (NDI), and orientation dispersion (ODI). We used ANCOVAs to compare between-groups and support vector modeling to investigate which variables (imaging, neurocognitive, motor) contribute the most to NF1 and unaffected participants distinction.

Results: After controlling for total brain volume, white matter volume was larger in the NF1 versus unaffected group with a large effect (partial η²=0.57). Cerebellar MD was higher in the NF1 group, while FA, NDI and ODI were lower in the NF1 group (p's < 0.05). Support vector modeling correctly classified 90.20% of participants as being in the NF1 or unaffected group. Top three weights were white matter volume, mobility ratings, and NDI.

Conclusions: Differences in cerebellar white matter microstructure (compared to unaffected youth) were identified in NF1. Cerebellar white matter volume, NDI, and MD were particularly useful differentiators between NF1 and unaffected youth and may be underlying mechanisms of cerebellum-mediated neurocognitive deficits in NF1.

Mutations in the transglutaminase 6 gene (TGM6) are associated with spinocerebellar ataxia type 35 (SCA35), and cases have been reported across diverse ethnic groups. We report the first documented case of SCA35 in Saudi Arabia, together with a focused literature review. A 35-year-old Saudi man presented to a neurology clinic with severe gait instability following nonspecific symptoms, including unintentional weight loss, dysphagia, abdominal pain, and intermittent diplopia. No family history of ataxia or similar neurological disease was noted. The condition progressed with neuropsychiatric manifestations (adjustment disorder, generalized myalgia, fibromyalgia) and upper motor neuron and extrapyramidal signs. He was admitted for further evaluation. A comprehensive diagnostic work-up, including cerebrospinal fluid studies, multiplex polymerase chain reaction, and nerve conduction studies, ruled out celiac disease, Wilson's disease, and demyelinating diseases. Brain and full-spine magnetic resonance imaging showed no cerebellar atrophy or spinal cord abnormalities. Whole-exome sequencing identified a heterozygous splice-site mutation in TGM6 (c.850 + 1G > A), consistent with autosomal dominant SCA35. To our knowledge, this is the first reported case of SCA35 in the Middle East. This case underscores the challenges in diagnosing this condition, as patients may present with atypical features, such as dysphagia. Our findings enhance the current understanding of the epidemiology, clinical manifestations, and genetic landscape of SCA35 to improve the diagnosis and management of this rare disorder.